Androgen signaling and kinase regulation in PCA

描述（由申请人提供）：本提案基于雄激素通过激活基因表达和激酶级联诱导细胞反应的假设。前者被广泛认可，因为雄激素受体本身是一个转录因子。后者近年来开始受到重视，主要是由于认识到磷酸化是几乎所有细胞过程的一个组成部分。然而，这两种机制并不相互排斥，因为转录激活可导致激酶或磷酸酶的上调，从而直接影响磷酸化信号传导。目前的建议是关于一个新的丝氨酸激酶，是由雄激素转录激活，并反过来调节雄激素受体活性。与正常的前列腺癌细胞相比，它通常在前列腺癌细胞中过度表达。它是男性细胞特异性的，似乎是来自雄激素和生长因子的信号的整合者。

DESCRIPTION (provided by applicant): The present proposal is based on the hypothesis that androgen induces cellular responses via the activation of both gene expression and kinase cascade. The former is widely recognized, since the receptor for androgen itself is a transcriptional factor. The latter has begun to be appreciated in recent years, largely due to the realization that phosphorylation is an integral part for virtually all cellular processes. These two mechanisms however are not mutually exclusive, as transcriptional activation can lead to upregulation of kinases or phosphatases, thereby directly influencing the phosphorylatiion signaling. The present proposal is concerned with a novel serine kinase that is transcriptionally activated by androgen and that in turn regulates androgen receptor activity. It is generally overexpressed in prostate cancer cells, compared to normal counterpart. It is male-cell speciic and appears to be an integrator of signals coming from androgen and growth factor. There are three specific aims of the proposal: 1. To characterize MAK as a target of androgen activation. 1. To characterize MAK as a regulator of androgen receptor. 1. To characterize MAK as a modulator of androgen prostate cancer growth.